The SARS-CoV-2 pandemic has resulted in close to 1,000,000 deaths worldwide in less than one year (1) with an upcoming influenza season, raising the prospect of complications resulting from co-infections. Our understanding of gene expression in patients with viral co-infection is limited. We mined published microarray data (2) to identify transcriptional features most significantly associated with viral co-infection. We identified the cytokine interleukin-16 as among the most differentially expressed genes in the blood of patients with viral co-infections, including in a patient with co-infection of influenza A and human coronavirus OC43 and in a patient with co-infection of influenza A and human coronavirus 229E. Interleukin-16 may be relevant to the biology of viral co-infection.